Genes encoded within the major histocompatibility complex (MHC) and T cell antigen receptor (TCR) gene complexes have been shown to play important roles in immune responses and in susceptibility to autoimmune diseases. The contribution of individual gene products within these gene complexes and the mechanisms by which they function have not been elucidated. In the present studies, inheritance patterns of HLA and T cell receptor (TCRA and TCRB) genes were analyzed in families. Structural analyses have led to a refined estimate of the extent of the germline TCRBV repertoire and to the identification of polymorphic gene segments and regions. Two frequently occurring insertion/deletion related polymorphisms (IDRP) were found in the TCRB gene complex; one involves a stretch of 21.5kb in the V region and another spans about 20kb near the C region. Three TCRBV genes are encoded in the inserted TCRBV region; BV7S3, BV9S2(P), and a second copy of BV13S2 which is identical to a gene present in all haplotypes. The inserted region shows a pattern of sequence identity with other regions of the gene complex that suggests genetic mechanisms for its origin may include unequal crossing over, gene conversion like events, insertion and deletion of short segments of DNA and mutation. Deleted haplotypes contain 60 genes of which 50 are functional, whereas, inserted haplotypes contained 63 gene of which 52 are functional. Three BV genes were found to have null or unexpressed alleles. The utilized TCR repertoire was analyzed in specific immune responses. The TCR present on T cell lines with defined specificities were characterized and the extent of junctional diversity associated with each TCRBV family was determined. Oligoclonal populations of T cells expressing a few BV families were present on T cells responding to Hepatitis surface antigen. The BV genes used by different responder individuals were similar. Activated cells from patients with autoimmune diseases were analyzed in a similar fashion. Patients with Kawasaki's disease showed oligoclonal expansion of several BV families. Detailed knowledge of the extent and diversity of the germline TCR repertoire will greatly facilitate our ability to understand the role of TCR genes in immune responses in normal and disease states.